Interferon-beta regulates cytokines and BDNF: greater effect in relapsing than in progressive multiple sclerosis.

The mechanism of action of interferon (IFN)-beta therapy in multiple sclerosis (MS) is only partially known, and its efficacy changes with disease stage. In different forms of MS, we determined how IFN-beta regulates mononuclear cell production of the important anti-inflammatory Th2 cytokine - IL-10, the Th1 cytokine - IFN-gamma, and the brain-derived neurotrophic protein - BDNF. Activated T cells and monocytes from therapy-naïve patients secreted more IL-10 than healthy controls. During IFN-beta therapy, however, T cells produced less IL-10. In vitro, IFN-beta stimulated IL-10 production by activated T cells, but inhibited IL-10 secretion by activated monocytes, a richer source of IL-10 than T cells. The form of MS also affected cytokine production. IL-10 and BDNF levels in MNC were high during relapsing/remitting (RR) MS, but low in progressive MS. Surprisingly, IFN-beta therapy increased BDNF levels in antidepressant-naïve patients, but BDNF was lower during concurrent antidepressant drug therapy, suggesting an interaction between MS, depression, and neurodegeneration. IFN-beta in vitro strongly induced IL-10 and IFN-gamma in activated T cells in RRMS, but not in progressive MS, suggesting IFN resistance. IFN-beta effects are specific for disease state and immune subsets, possibly explaining why IFN-beta therapy is most effective in early T cell-regulated RRMS, but less beneficial in progressive MS, where chronic plaques contain few T cells and high numbers of monocytes.

Effect of methylphenidate on auditory event related potential in boys with attention deficit hyperactivity disorder.

OBJECTIVE: Event related brain potentials (ERPs) is a non-invasive technique giving knowledge about neural activity associated with sensory and cognitive information processing. The aims of the present study were to investigate amplitude and latency of P100, N200, and P300 in parietal and frontal areas in children with attention deficit hyperactivity disorder (ADHD), and in healthy children, and to determine the effect of methylphenidate (MPH) on these ERPs indices in ADHD group. METHODS: ERP indices, latencies of parietal P3 (PP3L), P1 (PP1L), N2 (PN2L), and frontal P1 (FP1L), N2 (FN2L), P3 (FP3L), and amplitudes of parietal P3 (PP3A), P1 (PP1A), N2 (PN2A), and frontal P1 (FP1A), N2 (FN2A), and P3 (FP3A), using an auditory oddball paradigm were recorded before and under MPH treatment in boys with ADHD, and in 23 healthy children. RESULTS: Before MPH treatment, PP3L was significantly longer and PP3A, PN2A, FN2A, and FP3A smaller in children with ADHD compared to healthy children (all P values < .05). No significant difference was found in PP1L, PP1A, PN2L, FP1L, FP1A, FN2L, and FP3L between ADHD and control group (all P values > .05). MPH treatment resulted in a significant decrease in PP3L, PN2L, and FP3L, and increase in PP3A, PP1A, and FP3A (all P values < .05). There was no significant difference in PP1L, PN2A, FP1L, FP1A, FN2L, and FN2A between before MPH and under MPH treatment in ADHD subjects (all P values > .05). Under MPH treatment, PP3L, PP3A, PP1L, PP1A, PN2L, FP1L, FP1A, FN2L, FP3L, and FP3A were not significantly different between children with ADHD and healthy controls (all P values > .05). However, PN2A and FN2A were significantly smaller in ADHD subjects compared to controls (both P values < .05). CONCLUSION: This study provides indirect evidence that ADHD subjects are associated with abnormalities in signal detection (inattention) and discrimination, and information processing. In addition, present study has shown that except FN2A and PN2A, MPH normalizes ERP indices, which suggested that MPH may be effective on impaired information processing in ADHD, but not on the receiving information.

Median nerve somatosensory evoked potentials recorded with cephalic and noncephalic references in central and peripheral nervous system lesions.

Somatosensory evoked potentials (SSEP) to electrical stimulation of the median nerve by using cephalic and noncephalic references were studied to detect the generator sources of short latency evoked potentials in 29 patients with cerebral, brainstem, spinal and peripheral nerve lesions. Patients were divided into six groups according to the localization of their lesions: group 1: cortical and subcortical lesions, group 2: basal ganglion lesions, group 3: pons and mesencephalon lesions, group 4: diffuse cerebral lesions, group 5: cervical cord lesions, group 6: brachial plexus lesions. Potentials were recorded using cephalic and noncephalic references after median nerve stimulation. Evidence obtained from patients suggested the following origins for these short latency SSEPs: P9 may arise in brachial plexus, P11 in dorsal basal ganglions or dorsal column, P13 and P14 in the nucleus cuneatus and lemniscal pathways, N16 in subthalamic structures and most likely mid and lower pons, N18 from the thalamus and thalamocortical tract, and N20 from primary somatosensory cortex.

Auditory brainstem responses in children with congenital heart disease.

BACKGROUND: Cyanotic congenital heart diseases usually lead to growth and developmental delay in children due to chronic hypoxemia and undernourishment that may affect the central nervous system. The auditory brainstem responses are determined to assess the maturation and function of the brainstem. Therefore, we used the auditory brainstem responses to investigate the effect of cyanotic congenital heart diseases on brainstem maturation. METHODS: The auditory brainstem responses were investigated in 45 children (23 cyanotic, 22 acyanotic) with congenital heart diseases and compared with the results of 30 healthy counterparts (all children were aged between 2 months and 15 years). RESULTS: The results of auditory brainstem responses were similar in acyanotic patients and in normal children. The cyanotic patients under 1 year of age had more prolonged I-V interpeak latencies than those of control and acyanotic patients (P < 0.05). There was no difference between all groups older than 1 year of age. In cyanotic children, I-V interpeak latencies showed significant negative correlation with arterial oxygen saturation and partial oxygen pressure (P < 0.05). CONCLUSIONS: Cyanotic congenital heart diseases may cause significant retardation on brainstem maturation due to chronic hypoxemia, especially in infants under 1 year of age, whereas acyanotic congenital heart diseases have no effect on auditory brainstem responses.